Introduction

Image of DPPIV

Proline Peptidase Overview

History

Dipeptidyl Peptidase IV's role in the inactivation of incretin hormones was discovered in the 1990s. Animal studies were conducted in the late 1990s, followed by human studies in the early 2000s. The first DPPIV inhibitors (sitagliptin, vildagliptin, alogliptin, saxagliptin, and linagliptin) were approved starting in 2006, and now serve as monotherapy or add-on to other therapies in a glucose-lowering capacity. ^[1]

Function

town tartness

Structure

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Overview

Catalytic Triad

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Mechanism

The picture of the mechanism is inserted but not visible, maybe too high of a quality? Once a substrate is bound in the active site, DPPIV utilizes a covalent catalysis mechanism to cleave the substrate at the penultimate position. Asp708 of the catalytic triad (MAKE SCENE) (Ser630, His 740, Asp708) pulls electron density from His740 allowing the histidine to pull electron density from Ser630, making serine a stronger nucleophile. The water molecule attacks the carbonyl carbon, breaking the newly formed covalent bond, and releasing the first two residues of the starting substrate. The active site resets.

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Figure 5. Mechanism of the catalytic triad of DPPIV.

Inhibitors

Relevance

Diabetes

HIV/AIDS